Project Summary/Abstract The stereoselective synthesis of C-C bonds is central to the field of organic synthesis. The ability to forge C-C bonds in an enantioselective fashion has been critical to the application of small molecules in medicinal chemistry. Since different enantiomers of the same molecule often have differential biological properties, pharmaceuticals are usually prepared as single enantiomers. Consequently, much effort has been expended on the develop enantioselective synthetic methods. The stereoselective a-alkylation of carbonyl compounds has been a workhorse reaction for the construction of C-C bonds with defined stereochemistry. The most robust methods employ chiral auxiliaries such as the Evan?s auxiliary. While these methods are functional, they have the disadvantage of requiring additional synthetic operations to install and remove the chiral auxiliaries. These additional steps can be significant impediments to developing cost effective and environmentally friendly syntheses of medicinal compounds. Catalytic enantioselective methods present an attractive alternative to these auxiliary based approaches. The proposed research outlines a strategy to develop an enantioselective a-alkylation via coupling of readily available aldehydes and organohalides enabled by the merger of enamine/photoredox catalysis with transition metal catalysis. The proposal will specifically seek to engage enaminyl radicals, generated via enamine/photoredox catalysis with transition metal catalysts, specifically nickel catalysts, to afford a net a-functionalization of aldehydes. The proposal details a plan to identify a suitable triple catalytic system. After identification of such a system, chiral amine catalysts and nickel complexes bearing chiral ligands will be investigated as a means to control enantioselectivity of these reactions. In parallel with these studies, multi-variable linear regression analysis techniques will be applied as a mechanistic tool to understand the origins of stereoselectivity in these reactions. Insights from these studies will inform both improved catalyst design and an understanding of the interactions responsible for selectivity in reactions intercepting radical intermediates. Overall, the proposed research will provide a platform for the catalytic enantioselective alkylation of aldehydes, which in turn will improve the syntheses of pharmaceuticals and enable the discovery of new medicinally active compounds.